A scalable approach to topographically mediated antimicrobial surfaces based on diamond.

Bio-inspired Topographically Mediated Surfaces (TMSs) based on high aspect ratio nanostructures have recently been attracting significant attention due to their pronounced antimicrobial properties by mechanically disrupting cellular processes. However, scalability of such surfaces is often greatly limited, as most of them rely on micro/nanoscale fabrication techniques. In this report, a cost-effective, scalable, and versatile approach of utilizing diamond nanotechnology for producing TMSs, and using them for limiting the spread of emerging infectious diseases, is introduced. Specifically, diamond-based nanostructured coatings are synthesized in a single-step fabrication process with a densely packed, needle- or spike-like morphology. The antimicrobial proprieties of the diamond nanospike surface are qualitatively and quantitatively analyzed and compared to other surfaces including copper, silicon, and even other diamond surfaces without the nanostructuring. This surface is found to have superior biocidal activity, which is confirmed via scanning electron microscopy images showing definite and widespread destruction of E. coli cells on the diamond nanospike surface. Consistent antimicrobial behavior is also observed on a sample prepared seven years prior to testing date.

Phytochemical constituents, biological activities, and health-promoting effects of the genus Origanum.

Origanum species are mostly distributed around the Mediterranean, Euro-Siberian, and Iran-Siberian regions. Since time immemorial, the genus has popularly been used in Southern Europe, as well as on the American continent as a spice now known all over the world under the name "oregano" or "pizza-spice." Origanum plants are also employed to prepare bitter tinctures, wines, vermouths, beer, and kvass. The major components of Origanum essential oil are various terpenes, phenols, phenolic acids, and flavonoids with predominant occurrence of carvacrol and thymol (with reasonable amounts of p-cymen and -terpinene) or of terpinene-4-ol, linalool, and sabinene hydrate. Many species of Origanum genus are used to treat kidney, digestive, nervous, and respiratory disorders, spasms, sore throat, diabetes, lean menstruation, hypertension, cold, insomnia, toothache, headache, epilepsy, urinary tract infections, etc. Origanum essential oil showed potent bioactivities owing to its major constituents' carvacrol, thymol, and monoterpenes. Several preclinical studies evidenced its pharmacological potential as antiproliferative or anticancer, antidiabetic, antihyperlipidemic, anti-obesity, renoprotective, antiinflammatory, vasoprotective, cardioprotective, antinociceptive, insecticidal, and hepatoprotective properties. Its nanotechnological applications as a promising pharmaceutical in order to enhance the solubility, physicochemical stability, and the accumulation rate of its essential oils have been investigated. However, Origanum has been reported causing angioedema, perioral dermatitis, allergic reaction, inhibition of platelet aggregation, hypoglycemia, and abortion. Conclusive evidences are still required for its clinical applications against human medical conditions. Toxicity analyses and risk assessment will aid to its safe and efficacious application. In addition, elaborate structure-activity studies are needed to explore the potential use of Origanum-derived phytochemicals as promising drug candidates.

Effect of Varying Amount of Polyethylene Glycol (PEG-600) and 3-Aminopropyltriethoxysilane on the Properties of Chitosan based Reverse Osmosis Membranes.

Chitosan and polyethylene glycol (PEG-600) membranes were synthesized and crosslinked with 3-aminopropyltriethoxysilane (APTES). The main purpose of this research work is to synthesize RO membranes which can be used to provide desalinated water for drinking, industrial and agricultural purposes. Hydrogen bonding between chitosan and PEG was confirmed by displacement of the hydroxyl absorption peak at 3237 cm-1 in pure chitosan to lower values in crosslinked membranes by using FTIR. Dynamic mechanical analysis revealed that PEG lowers Tg of the modified membranes vs. pure chitosan from 128.5 °C in control to 120 °C in CS-PEG5. SEM results highlighted porous and anisotropic structure of crosslinked membranes. As the amount of PEG was increased, hydrophilicity of membranes was increased and water absorption increased up to a maximum of 67.34%. Permeation data showed that flux and salt rejection value of the modified membranes was increased up to a maximum of 80% and 40.4%, respectively. Modified films have antibacterial properties against Escherichia coli as compared to control membranes.

Transfersomes: a Revolutionary Nanosystem for Efficient Transdermal Drug Delivery.

Transdermal delivery system has gained significance in drug delivery owing to its advantages over the conventional delivery systems. However, the barriers of stratum corneum along with skin irritation are its major limitations. Various physical and chemical techniques have been employed to alleviate these impediments. Among all these, transfersomes have shown potential for overcoming the associated limitations and successfully delivering therapeutic agents into systemic circulation. These amphipathic vesicles are composed of phospholipids and edge activators. Along with providing elasticity, edge activator also affects the vesicular size and entrapment efficiency of transfersomes. The mechanism behind the enhanced permeation of transfersomes through the skin involves their deformability and osmotic gradient across the application site. Permeation enhancers can further enhance their permeability. Biocompatibility; capacity for carrying hydrophilic, lipophilic as well as high molecular weight therapeutics; deformability; lesser toxicity; enhanced permeability; and scalability along with potential for surface modification, active targeting, and controlled release render them ideal designs for efficient drug delivery. The current review provides a brief account of the discovery, advantages, composition, synthesis, comparison with other cutaneous nano-drug delivery systems, applications, and recent developments in this area.

Evaluating the ion exchange chromatography for matrix-assisted PEGylation and purification of consensus interferon.

Scientists have implemented protein-PEGylation technology for boosting-up the pharmacokinetics and stability of recombinant therapeutic proteins. In the present study, (a) matrix-assisted PEGylation was compared with solution-phase PEGylation and (b) matrix-assisted PEGylation was performed with different ion exchange resins for impact of chromatography medium on yield and purity of PEGylated product. DEAE Sepharose CL 6B, DEAE Fracto gel, and Macro cap Q ion exchange chromatography medium were compared for on column PEGylation and purification of cIFN. A MSC-PEG of 12.0 KDa was selected. cIFN was bound to ion exchange medium, and PEG solution was passed through resin for 180 Min, and protein was eluted by sodium chloride linear gradient. Yield and purity for mono-PEGylated cIFN with Macro cap Q matrix was 75% and 99%, respectively, whereas for DEAE Sepharose was 45% and 60%. DEAE Fracto gelTM purity was 85% with 50% yield of mono-PEGylated cIFN. Further investigation of in vitro biological activities demonstrated that about 30% antiviral activity was reduced as compared to unmodified cIFN. However, thermal stability was significantly improved. The present study proved that matrix-assisted PEGylation can improve the yield and purity of mono-PEGylated product, and Macro Cap resin provided the highest yield of a homogeneous product. In present study, (a) matrix-assisted PEGylation was compared with solution-phase PEGylation and (b) matrix-assisted PEGylation was performed with different ion exchange resins for impact of chromatography medium on yield and purity of PEGylated product. Matrix-assisted PEGylation increases the yield of mono-PEGylated product and further Macro CapTM produced highest yield and purity of PEGylated cIFN.

Two-Stage Flexor Tendon Reconstruction in Zone II Using Paediatric Silicon Catheter at Mayo Hospital Lahore: A Case Series.

The aim of the study was to assess the functional outcomes after two stage flexor tendon reconstruction in zone II tendon injury of the hand using paediatric silicon catheter. A prospective case series of total 22 digits of 21 patients having Boyes grades I, II and III neglected flexor tendon injury, for a mean time of 10 months since injury were included. Two stage reconstructive procedure was performed. A final follow-up was done at one year to assess the functional outcome using Buck-Gramcko scale. Out of 22 digits, there were 06 (27.27%) Boyes grades I digits, 11 (50%) grades II and 5 (22.72%) grades III. At final follow-up thirteen (59.09%) digits had excellent, five (22.72%) had good while three (13.63%) had satisfactory result and one (4.54%) had poor result. We concluded that two stage flexor tendon reconstruction using silicon catheter yields good results and is cost effective.

Neurotoxic effects of titanium dioxide nanoparticles on the brain of male sprague dawley rats.

Titanium dioxide nanoparticles have diverse applications in many fields and are used in cosmetics, sterilization, paints, tooth paste, food products, air cleaning, sunscreens and waste water treatment plants due to their unique properties. But on the other hand, the wide use of titanium dioxide nanoparticles raises concerns to the upcoming challenges of human health. This study assessed the neurotoxic effect of titanium dioxide nanoparticles by histology, cell viability, oxidative stress and acetylcholine esterase level. For this purpose, 28 days old, post weaning male Sprague Dawley rats (n=25) were procured from the animal house of the Government College University, Faisalabad. Rats were randomly divided into five groups with five rats in each group and designated as Control (C) without treatment, Placebo group (S) treated with 0.9% normal saline and three nanoparticles treated groups (Group 1 of 80 mg/kg, Group 2 of 120 mg/kg and Group 3 of 160 mg/kg body weight of rat). Nanoparticles were injected intraperitonealy on alternate days for 28 days. On 29th day, rats were sacrificed and brain was isolated from all groups. Accumulation of titanium in the brain was assessed by inductively coupled plasma mass spectrometry (ICP-MS) and its increase in concentration was observed in a dose dependent manner. Cell viability, acetylcholine esterase and glutathione activities were significantly (P<0.05) decreased in Group 2 and Group 3 treated groups as compared to control and placebo groups. Histological alterations were also reported in brain exposed to titanium dioxide nanoparticles treated groups. This study revealed that titanium dioxide nanoparticles are neurotoxic as expressed by histological alterations, reduced cell viability, reduced acetylcholine esterase activity and induced oxidative stress by reducing glutathione activity in male Sprague Dawley rats.

PELLETS AND PELLETIZATION: EMERGING TRENDS IN THE PHARMA INDUSTRY.

The present time is considered as an era of advancements in drug delivery systems. Different novel approaches are under investigation that range from uniparticulate to multi particulate system, macro to micro and nano particulate systems. Pelletization is one of the novel drug delivery technique that provides an effective way to deliver the drug in modified pattern. It is advantageous in providing site specific delivery of the drug. Drugs with unpleasant taste, poor bioavailability and short biological half-life can be delivered efficiently through pellets. Their reduced size makes them more valuable as compared to the conventional drug deliv- ery system. Different techniques are used to fabricate the pellets such as extrusion and spheronization, hot melt extrusion, powder layering, suspension or solution layering, freeze pelletization and pelletization by direct compression method. Various natural polymers including xanthan gum, guar gum, tragacanth and gum acacia, semisynthetic polymers like cellulose derivatives, synthetic polymers like derivatives of acrylamides, can be used in pellets formulation. Information provided in this review is collected from various national and intemational research articles, review articles and literature available in the books. The purpose of the current review is to discuss pellets, their characterizations, different techniques of pelletization and the polymers with potential of being suitable for pellets formulation.

Controlled release matrix tablets of glipizide: Influence of different grades of ethocel and Co-excipient on drug release.

The aim of the current study was to formulate and evaluate glipizide controlled release matrix tablets by means of different grades of polymer Ethoceland different co-excipients in order to evaluate their effect on drug release profiles during in vitro dissolution studies. Type II diabetes mellitus is usually treated with Glipizide. Glipizide belongs to sulfonylurea group. Gastric disturbance and severe hypoglycemia has been observed after taking glipizide orally. To overcome these problems, controlled release matrices were developed using different grades of ethyl cellulose polymer with a drug-polymer ratio of 1:3by the direct compression method. The effect on drug release of partial replacement of lactose by different co-excipients, HPMC K100M, starch and CMC, were also studied. Diameter, thickness, hardness, friability, weight variations, drug contents of formulations were tested, these properties were within prescribed limits. Co-excipients and polymer containing formulations were compared to the without co-excipients and polymer containing formulations with respect to their release profile. After a 24-hour release study, ethyl cellulose polymer containing formulation exhibited prolonged release for 5-16 hours; however the polymer Ethocel (R) standard FP 7 Premium without co-excipient containing formulation exhibited controlled release for 24 hours. Incompatibility was investigated between drugs, co-excipient DSC and polymer study was performed and any type of interaction was not found. Different kinetic models were used to study the release mechanism. An enhanced release rate was observed in case of excipients containing formulations.

Probabilistic risk assessment of microplastics in Tai Lake, China.

Microplastics are a global environmental concern, especially in freshwater ecosystems. Despite the studies in specific regions of Tai lake, a gap persists in understanding the comprehensive risk of MPs across the entire watershed. Therefore, this study offers an overview of MPs abundance and assesses ecotoxicological risk by employing acute and chronic species sensitivity distributions, which consider the effects triggered by MPs. The concentrations of MPs ranged from 0 to 18.6 particles/L within the lake, 1.56 to 1.42 × 102 particles/L in the rivers, and 0.16 to 0.7 particles/L in the estuaries. Certain areas, particularly the northwest and southeast regions, exhibit higher concentrations. Using existing toxicity data, this study calculated predicted no effect concentrations for acute and chronic exposure of MPs to freshwater species, resulting in values of 11.5 and 31.72 particles/L, respectively. The probabilistic risk assessment indicates that the average risk possibility of MPs in Tai lake was 16 %. Moreover, the risk characterization ratio indicated that 22 % of the locations in Tai lake showed an acute ecological risk, while 7.4 % exhibit a chronic ecological risk. The assessment concluded that MPs reported in the literature could pose a considerable risk to Tai lake biota. However, the risk associated with MPs followed descending order: river >lake > estuary waters. Our research supplies valuable insights for the assessment of ecological risks associated with MPs on a whole watershed scale.

Herbal Treatments for Obesity: A Review.

Obesity is the most pervasive metabolic disorder, further linked with many other diseases, including diabetes, hypertension, cardiovascular disorders, and sleep apnea. To control the increasing weight of obese individuals, experts usually recommend exercise and lifestyle alterations, but medication and surgeries are also advised in severe cases. FDA-approved obesity-controlling drugs are effective but possess certain adverse effects, including dry mouth, drug abuse, dysregulation in monoamine neurotransmitters, insomnia, and many more. Medication processes are expensive; researchers have focused on safer and more effective alternative approaches than pharmaceutical drugs. Since ancient times, a diverse array of herbal plants have been used due to their therapeutic effect, as in-vitro and in-vivo experimentations have proved the effectiveness of herbal plants with no mortality. In this review, we have presented various herbs with their metabolically active secondary metabolites, including Berberis vulgaris L, Rhizoma Coptidis, Radix Lithospermi, Aloe vera, Clerodendrum multiflorum Burm f., Astragalus membranaceus (Fisch), Boerhaavia diffusa, Achyranthes aspera L., etc. All of these herbs are responsible for anti-obesity, anti-diabetic, and anti-inflammatory effects. Most of the previously published clinical trials and animal studies that confirmed the significant potential of these herbal plants and their active ingredients to reduce weight by decreasing the accumulated fats in the body have also been discussed in this review. Thus, it is concluded that scientists must consider and utilize these natural treasures for safe, effective, and cost-effective treatment. It will open new and novel ways for treatment regimes.

Association of Oral Submucous Fibrosis Risk with GSTM1 and GSTT1 Gene Polymorphisms.

OBJECTIVE: To determine the association of GSTM1 and GSTT1 polymorphisms with oral submucous fibrosis (OSF). STUDY DESIGN: A case-control study. Place and Duration of the Study: Department of Human Genetics and Molecular Biology, University of Health Sciences, Lahore and Oral and Maxillofacial Surgery Department, de Montmorency, College of Dentistry/ Punjab Dental Hospital, Lahore, Pakistan, from 1st April 2019 to 31st April 2020. METHODOLOGY: OSF patients were diagnosed with different clinical staging of mouth opening by Vernier caliper with the help of a professional dentist in the Department of Oral and Maxillofacial, de Montmorency, College of Dentistry, Lahore. One hundred and eight blood samples of OSF patients and 108 samples of normal controls were collected. Genomic DNA was obtained from whole-blood extraction. Multiplex PCR amplification using GSTM1, GSTT1, and ß -Globin gene primers was performed. RESULTS: GSTM1 and GSTT1 null genotypes frequencies were found in 43.5% (47/108) and 13.9% (15/108) of controls, whereas 54.6% (59/108) and 25.9% (28/108) of OSF patients, respectively. OSF patients had a greater frequency rate of GSTM1 and GSTT1 null genotypes than controls [OR 1.56, 95% CI 0.91-2.67 (p=0.13)] and [OR 2.17, 95% CI 1.08-4.34 (p=0.04)], respectively. The GSTT1 genotype was found statistically significant with OSF (p=0.05), and risk was also determined. The cumulative effect of null genotypes of GSTM1/GSTT1 did not show any association with the controls and in OSF patients. Proportions of active and null alleles of the patient group were; 86.1%/13.9%; and in control, it was 92.6%/7.4% (OR = 2.01; CI: 0.82-4.97; p=0.18), respectively. CONCLUSION: The study determined a statistically significant association of GSTT1 gene polymorphism with OSF. KEY WORDS: Oral submucous fibrosis, GSTM1, GSTT1, Gene polymorphisms, Genetic risk.

Design and development of insulin emulgel formulation for transdermal drug delivery and its evaluation.

The objective of the present study was to formulate an insulin emulgel, selection of an optimize formulation through in vitro drug release kinetics and finally evaluate its hypoglycemic activity in animal model. Insulin emulgel was prepared using emu oil as penetration enhancer with the combination of carbomer or hydroxypropyl methylcellulose (HPMC) as gelling agent and polysorbate 80 as emulsifier. The response of gelling agent type (carbomer or HPMC) and concentration of other two variables penetration enhancer and emulsifier were studied using 2(3)factorial design during in vitro drug release through excised rat skin. Biological activity of emulgel formulation was also investigated using Albino rabbits alone and in combination with iontophoresis. The in vivo efficacy of insulin emulgel was assessed by measuring the blood glucose level at start of the experiment and after every 15 minutes interval for 120 minutes. Total eight formulations were studied. F4 formulation showed maximum insulin permeation flux (4.88 ± 0.09 µg/cm(2)/hour) through excised rat skin. Insulin permeation from these formulations was found to follow the Korsmeyer-Peppas model (r(2) =0.975 to 0.998) during 24 hour with non-Fickian mechanism. Formulation F4 was further investigated in Albino rabbits. For the first group (treated with insulin emulgel alone) the blood glucose level decreased from initial value 250±10mg/dl to 185±7mg/dl at 120 minutes and for the second group (treated with insulin emulgel plus iontophoresis) the blood glucose level decreased to 125±5mg/dl in 120 minutes (P<0.05). It was observed that absorption of insulin through transdermal emulgel was greater in combination with iontophoresis to decrease blood glucose level. On the basis of this study, it has been shown that application of insulin emulgel iontophoretically can be used as alternative (acceptable & painless) to injectable insulin subject to further studies on large animals.

Microplastics in Tai lake food web: Trophic transfer and human health risk assessment.

Although microplastics (MPs) in marine organisms have been widely studied, the toxicity of MPs in freshwaters and human health is still a global challenge. To fill this gap, we implemented an Ecopath and food web accumulation model to simulate the Tai Lake ecosystem, a region dependent on the tourism and seafood industries. Our results suggested the accumulation of MPs throughout the food web and ultimately reach organisms at high trophic levels, including human-being, who consume MPs through seafood. The adults were prone to consume more MPs than adolescents and children. Unlike clams, fish biota magnification factors indicated that MPs accumulation between specific predator-prey interactions is not expected. The abundance of MPs within clams reveals a potential risk of MPs entering the food web. To better understand the MPs transfer, we recommend paying greater attention to species-specific mechanisms and the resources they rely on.

Tumor micro-environment sensitive release of doxorubicin through chitosan based polymeric nanoparticles: An in-vitro study.

Conventional chemotherapy poses toxic effects to healthy tissues. A therapeutic system is thus required that can administer, distribute, metabolize, and excrete medicine from human body without damaging healthy cells. This is possible by designing a therapeutic system that can release drug at specific target tissue. In current work, novel chitosan (CS) based polymeric nanoparticles (PNPs) containing N-isopropyl acrylamide (NIPAAM) and 2-(di-isopropyl amino) ethyl methacrylate (DPA) are designed. The presence of available functional groups i.e. OH- (3262 cm-1), -NH2 (1542 cm-1), and CO (1642 cm-1), was confirmed by Fourier Transform Infra-red Spectrophotometry (FTIR). The surface morphology and average particle size (175 nm) was determined through Scanning Electron Microscope (SEM). X-Ray Diffractometry (XRD) studies confirmed the amorphous nature and excellent thermal stability of PNPs up to 100 °C with only 2.69% mass loss was confirmed by Thermogravimetric analysis (TGA). The pH sensitivity of such PNPs for release of encapsulated doxorubicin at malignant site was investigated. The encapsulation efficiency of PNPs was 89% (4.45 mg/5 mg) for doxorubicin (a chemotherapeutic) measured by using UV-Vis Spectrophotometer. The drug release profile of loaded PNPs was 88% (3.92 mg/4.45 mg) at pH 5.3, in 96 h. PNPs with varying DPA concentration can effectively be used to deliver chemotherapeutic agents with high efficacy.

Quince seed mucilage/ß-cyclodextrin/Mmt-Na+-co-poly (methacrylate) based pH-sensitive polymeric carriers for controlled delivery of Capecitabine.

In current work, quince seed mucilage and ß-Cyclodextrin based pH regulated hydrogels were developed using aqueous free radical polymerization to sustain Capecitabine release patterns and to overcome its drawbacks, such as high dose frequency, short half-life, and low bioavailability. Developed networks were subjected to thermal analysis, Fourier transforms infrared spectroscopy, powder x-ray diffraction, elemental analysis, scanning electron microscopy, equilibrium swelling, and in-vitro release investigations to assess the network system's stability, complexation, morphology, and pH responsiveness. Thermally stable pH-responsive cross-linked networks were formed. Nanocomposite hydrogels were prepared by incorporating Capecitabine-containing clay into the swollen hydrogels. All the formulations exhibited equilibrium swelling ranging from 67.98 % to 92.98 % at pH 7.4. Optimum Capecitabine loading (88.17 %) was noted in the case of hydrogels, while it was 74.27 % in nanocomposite hydrogels. Excellent gel content (65.88 %-93.56 %) was noticed among developed formulations. Elemental analysis ensured the successful incorporation of Capecitabine. Nanocomposite hydrogels released 80.02 % longer than hydrogels after 30 h. NC hydrogels had higher t1/2 (10.57 h), AUC (121.52 µg.h/ml), and MRT (18.95 h) than hydrogels in oral pharmacokinetics. These findings imply that the pH-responsive carrier system may improve Capecitabine efficacy and reduce dosing frequency in cancer therapy. Toxicity profiling proved the system's safety, non-toxicity, and biocompatibility.

Cellulose acetate based sustainable nanostructured membranes for environmental remediation.

Membrane-based gas separation has a great potential for reducing environmentally hazardous carbon dioxide (CO2) gas. The polymeric membranes developed for CO2 capturing have some limitations in their selectivity and permeability. There is a need to overcome these issues and developed such membranes having high-performance CO2 capture with cost-effectiveness. The present study aimed to synthesize mixed matrix membranes (MMMs) having improved properties CO2 adsorption performance and stability than that of pure polymer. Further, the effect on CO2 adsorption by increasing the filler concentration in MMMs was investigated. The MMMs were synthesized by incorporating (1-5 wt%) Cu-MOF-GO composites as filler into cellulose-acetate (CA) polymer matrix by adopting the solution casting method. The performance of MMMs was studied by changing the Cu-MOF-GO composite concentration (1-5 wt%) in the polymer matrix at 45 °C up to 15 bar. Morphological analysis by using SEM confirms that by increasing the concentration of Cu-MOF-GO more than 3% will result in their agglomeration in MMM. The successful incorporation of MOF within the polymer matrix of MMMs was confirmed through the presence of functional groups using FTIR and Raman spectroscopy. XRD analysis revealed that pure CA changes its semi-crystalline behaviour into crystalline by the addition of Cu-MOF-GO. The maximum tensile stress and strain rate of MMMs was 45.1 N/mm2 and 12.8%. In addition, with an increase in (4-5 wt%) Cu-MOF-GO concentration the hydrophilicity of MMMs decreases. The maximum uptake rate of CO2 was 1.79 mmol/g and 7.98 wt% at 15 bar. The adsorption results conclude that Cu-MOF-GO composite and CA-based MMM can be effective for CO2 capture.

Angiogenic potential and wound healing efficacy of chitosan derived hydrogels at varied concentrations of APTES in chick and mouse models.

Chitosan (Cs) based biomaterials seem to be indispensable for neovasculogenesis and angiogenesis that ensure accelerated wound healing. Cs/poly (vinyl alcohol) (PVA) bio-constructs were cross-linked and investigated with varying concentrations of aminopropyltriethoxysilane (APTES). This study comprised of three phases: fabrication of hydrogels, characterization, assessment of angiogenic potential along with toxico-pathological effects, wound healing efficacy in chick and mice, respectively. The hydrogels were characterized by FTIR, SEM and TGA and the swelling response was examined in different solvents. The hydrogels swelling ratio was decreased with increasing amount of APTES, showed the highest swelling at acidic and basic pH while low swelling at neutral pH. Chorioallantoic membranes (CAM) assay was performed to study in-vivo angiogenesis, toxicological, morphological, biochemical and histological analyses in developing chicks. The results showed remarkably improved angiogenesis with little deviations in morphological, histological features and liver enzymes of chick embryos at higher concentrations of APTES. Besides, full thickness wounds were excised on mice dorsolateral skin to assess the wound healing. The rate of wound size reduction was significantly higher after topical application of hydrogels with elevated levels of crosslinker. Hence, the hydrogels showed enhanced angiogenesis, accelerated wound healing with little or no observable in-vivo toxicity.

A quadruple blinded placebo controlled randomised trial to evaluate the effectiveness of an Iodine complex for patients with mild to moderate COVID-19 in Pakistan (I-COVID-PK): A structured summary of a study protocol for a randomised controlled trial.

OBJECTIVES: The objective of the study is to measure the efficacy of ionic-iodine polymer complex [1] for clinical and radiological improvement in coronavirus disease 2019 (COVID-19) patients. TRIAL DESIGN: The trial will be closed label, randomized and placebo-controlled with a 1:1:1:1 allocation ratio and superiority framework. PARTICIPANTS: All PCR confirmed COVID-19 adult patients including non-pregnant females, with mild to moderate disease, will be enrolled from Shaikh Zayed Post-Graduate Medical Complex, Ali Clinic and Doctors Lounge in Lahore (Pakistan). Patients with any pre-existing chronic illness will be excluded from the study. INTERVENTION AND COMPARATOR: In this multi-armed study ionic-iodine polymer complex with 200 mg of elemental iodine will be given using three formulations to evaluate efficacy. Patients will be receiving either encapsulated iodine complex of 200 mg (arm A), iodine complex syrup form 40 ml (arm B), iodine complex throat spray of 2 puffs (arm C) or empty capsule (arm D) as placebo; all three times a day. All the 4 arms will be receiving standard care as per version 3.0 of the clinical management guidelines for COVID-19 established by the Ministry of National Health Services of Pakistan. MAIN OUTCOMES: Primary outcomes will be viral clearance with radiological and clinical improvement. SARS-CoV-2 RT-PCR and HRCT chest scans will be done on the admission day and then after every fourth day for 12 days or till the symptoms are resolved. RT-PCR will only be shown as positive or negative while HRCT chest scoring will be done depending on the area and severity of lung involvement [2]. Time taken for the alleviation of symptoms will be calculated by the number of days the patient remained symptomatic. 30-day mortality will be considered as a secondary outcome. RANDOMISATION: Stratification for initial COVID-19 status (or days from initial symptoms as a proxy), age groups, gender, baseline severity of symptoms and co-morbidities will be used to ensure that the study arms remain balanced in size for the 1:1:1:1 allocation ratio. Randomization will be done using the lottery method. As patients are being admitted at different times, they will be recruited after obtaining their voluntary written informed consent following all standard protocols of the infection, control and disinfection. BLINDING (MASKING): This is a quadruple (participants, care providers, investigators and outcomes assessors) blinded study where only the study's Primary Investigator will have information about the arms and their interventions. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): 200 patients will be randomized into four groups with three experimental and one placebo arm. TRIAL STATUS: Protocol Version Number is 2.3 and it is approved from IRB Shaikh Zayed Hospital with ID SZMC/IRB/Internal0056/2020 on July 14th, 2020. The recruitment is in progress. It was started on July 30, 2020, and the estimated end date for the trial is August 15, 2021. TRIAL REGISTRATION: Clinical Trial has been retrospectively registered on www.clinicaltrials.gov with registration ID NCT04473261 dated July 16, 2020. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). With the intention of expediting dissemination of this trial, the conventional formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines.

Indications and clinical outcomes of fully covered self-expandable metallic tracheobronchial stents in patients with malignant airway diseases.

BACKGROUND: Airway stenting is an efficacious approach in management of malignant airway disease (MAD) with improvement in survival outcome. OBJECTIVE: To determine the indications and long-term clinical outcomes of tracheobronchial stenting in patients with MAD. METHODS: A cross-sectional review of 51 patients who underwent airway stenting from June 2011 to June 2019 was done. Paired t-test was used to compare mean difference of clinical characteristics between pre- and post-airway stenting. Kaplan-Meier curves were used to assess overall survival. RESULTS: A total of 51 patients had stent insertion with mean age 46.63±17.10years including 27(52.9%) females. Mainly 37(72.5%) patients had esophageal and 06(11.8%) had lung cancer. The main indications were bronchial stenosis 18(35.3%), tracheal stenosis 11(21.6%) and Tracheo-esophageal/bronchial fistula 13(25.5%). Obstruction was intrinsic, extrinsic and mixed in 20(39.2%), 13(25.5%) and 5(9.8%) patients, respectively. There was statistically significant mean difference in pre- and post-procedure oxygen saturation (mean (M)=89.8, standard deviation (SD)=6.70 vs M =95.5,SD=2.54.p =0.001) and performance status (M =3.65,SD =0.6 vs M =2.59, SD=0.83.p =0.001). Overall median survival was 16±3.44 weeks, highest amongst patients with intrinsic obstruction (27±6.51 weeks). CONCLUSION: Airway stenting is an effective endoscopic procedure to re-establish airway patency in MAD with minimal complications..